Details of the Drug Combination

General Information of Drug Combination (ID: DC9LLTD)

• Drug Combination Name: Vemurafenib + Dacarbazine
• Indication: Cutaneous melanoma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Dacarbazine (DMNPZL4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SK-MEL-28
  Zero Interaction Potency (ZIP) Score: 9.31
  Bliss Independence Score: 8.77
  Loewe Additivity Score: 3.83
  LHighest Single Agent (HSA) Score: 10.33

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vemurafenib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]

Vemurafenib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[7]

Vemurafenib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

Vemurafenib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Vemurafenib Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Affects Expression	[5]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[12]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[6]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[14]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[12]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[15]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[5]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[5]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[16]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[5]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[17]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[18]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[19]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[17]

Indication(s) of Dacarbazine

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[3]
Astrocytoma	2A00.0Y	Approved	[3]
Brain disease	8C70-8E61	Approved	[3]
Central nervous system disease	8A04-8D87	Approved	[3]
Glioblastoma	2A00	Approved	[3]
Gliosarcoma	N.A.	Approved	[3]
Melanoma	2C30	Approved	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]
Neuroblastoma	2D11.2	Investigative	[3]

Dacarbazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[21]

Dacarbazine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[22]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[23]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[24]

Dacarbazine Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Increases Expression	[25]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[20]
Interferon regulatory factor 1 (IRF1)	OT43DI6J	IRF1_HUMAN	Increases Expression	[26]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Activity	[27]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Response To Substance	[28]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[29]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Response To Substance	[30]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Response To Substance	[31]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Response To Substance	[31]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Affects Response To Substance	[32]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1)	OTS3FVTY	M3K1_HUMAN	Decreases Response To Substance	[31]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Decreases Response To Substance	[33]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DCR89Q5	MDA-MB-468	Investigative	[34]
Carcinoma	DCM1TTK	MCF7	Investigative	[34]
Colon adenocarcinoma	DC0A2KM	COLO 205	Investigative	[34]
Invasive ductal carcinoma	DC7IVWS	BT-549	Investigative	[34]
Invasive ductal carcinoma	DCQNMCX	T-47D	Investigative	[34]
Invasive ductal carcinoma	DCT7CY8	HS 578T	Investigative	[34]
Adenocarcinoma	DC1IWZQ	OVCAR3	Investigative	[1]
Adenocarcinoma	DCUS1SA	HCT-15	Investigative	[1]
Adult T acute lymphoblastic leukemia	DC05QQO	MOLT-4	Investigative	[1]
Amelanotic melanoma	DCCCS63	M14	Investigative	[1]
Chronic myelogenous leukemia	DC36LWS	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCOUX7J	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DC2VNAL	CAKI-1	Investigative	[1]
Glioma	DCGURRG	SF-295	Investigative	[1]
Glioma	DCBNDYL	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCHO2UV	OVCAR-8	Investigative	[1]
Large cell lung carcinoma	DC1VBZM	NCI-H460	Investigative	[1]
Malignant melanoma	DCTJ919	UACC62	Investigative	[1]
Malignant melanoma	DC3A3M2	LOX IMVI	Investigative	[1]
Melanoma	DCLKA7T	UACC-257	Investigative	[1]
Melanoma	DCTWX7M	SK-MEL-2	Investigative	[1]
Melanoma	DCQLPX0	MALME-3M	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCOW5VF	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DCR8L8N	ACHN	Investigative	[1]
Plasma cell myeloma	DCWAQTC	RPMI-8226	Investigative	[1]

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